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In patients with severe sepsis, albumin replacement in addition to crystalloid administration conferred no benefit, as compared with crystalloids alone, with respect to mortality at 28 or 90 days. Post hoc analysis suggested a possible benefit in patients with septic shock. For decades, human albumin has been administered to patients to provide adequate oncotic pressure and intravascular volume. 1 In 1998, however, a report from the Cochrane Injuries Group Albumin Reviewers indicated that the administration of albumin may be potentially harmful in critically ill patients, as compared with the administration of crystalloid solutions. 2 Subsequent meta-analyses reported contradictory findings. 3 , 4 To clarify this issue, a large, double-blind, randomized trial (the Saline versus Albumin Fluid Evaluation [SAFE] study) 5 was conducted, in which 4% albumin solution was compared with normal saline as fluid replacement in critically ill patients, with results indicating that albumin administration was . . .

Traumatic brain injury (TBI) represents a common and severe medical condition necessitating prompt risk stratification to enhance patient outcomes. Although substantial research has been conducted on the prognostic utility of various biomarkers for TBI, no single biomarker has been definitively recognized as the most precise predictor of disease outcomes. In comparison to other markers, the neutrophil-albumin ratio (NAR) has emerged as a cost-effective and reproducible inflammatory biomarker, demonstrating potential in evaluating the severity of inflammation and prognosticating outcomes in infections and cerebrovascular diseases. This study evaluated the prognostic significance of the NAR in comparison to two other readily accessible and cost-effective composite indices: the Neutrophil-Lymphocyte Ratio (NLR) and the Platelet-Lymphocyte Ratio (PLR) in individuals with TBI. We conducted a retrospective cohort analysis involving 297 hospitalized TBI patients, gathering comprehensive demographic, anthropometric, medical, clinical, laboratory, and imaging data to assess the expression changes of these biomarkers. Our findings suggest that both the NAR and the NLR possess predictive value regarding prognosis following TBI. However, receiver operating characteristic (ROC) curve analysis revealed that NAR outperformed NLR as a prognostic predictor. In conclusion, our examination of blood biochemistry composite indicators indicates that, while both NAR and NLR serve as significant prognostic markers, NAR is a more effective predictor of outcomes in patients with TBI.

Background Multiple imputation is a commonly used method for handling incomplete covariates as it can provide valid inference when data are missing at random. This depends on being able to correctly specify the parametric model used to impute missing values, which may be difficult in many realistic settings. Imputation by predictive mean matching (PMM) borrows an observed value from a donor with a similar predictive mean; imputation by local residual draws (LRD) instead borrows the donor’s residual. Both methods relax some assumptions of parametric imputation, promising greater robustness when the imputation model is misspecified. Methods We review development of PMM and LRD and outline the various forms available, and aim to clarify some choices about how and when they should be used. We compare performance to fully parametric imputation in simulation studies, first when the imputation model is correctly specified and then when it is misspecified. Results In using PMM or LRD we strongly caution against using a single donor, the default value in some implementations, and instead advocate sampling from a pool of around 10 donors. We also clarify which matching metric is best. Among the current MI software there are several poor implementations. Conclusions PMM and LRD may have a role for imputing covariates (i) which are not strongly associated with outcome, and (ii) when the imputation model is thought to be slightly but not grossly misspecified. Researchers should spend efforts on specifying the imputation model correctly, rather than expecting predictive mean matching or local residual draws to do the work.

Background and Objectives: Ischemia-modified albumin (IMA) has previously been identified as a biomarker for early ischemia, rapidly formed by acidosis and free radical modification of the N-terminus of human serum albumin. This study aimed to compare albumin and IMA levels in blood and cerebrospinal fluid (CSF) from 30 patients with spontaneous subarachnoid hemorrhage (SAH) and 15 patients with normal pressure hydrocephalus (NPH) at a single center between 2021 and 2022. Materials and methods: This prospective study included 30 patients diagnosed with subarachnoid hemorrhage (SAH), confirmed radiologically, who were admitted to the Health Sciences University İzmir Bozyaka Training and Research Hospital and constituted the study group. The control group consisted of 15 patients diagnosed with normal pressure hydrocephalus (NPH) without a history or radiological evidence of subarachnoid hemorrhage or any other intracranial hemorrhagic pathology. In the control group, no pathological findings suggestive of hemorrhage or inflammation were detected in serum or cerebrospinal fluid (CSF) analyses. Blood and CSF samples were collected simultaneously from all participants, and albumin and ischemia-modified albumin (IMA) levels were measured. Serum and CSF albumin and IMA levels were compared between the study and control groups. Results: Of the 30 patients included in the study, 19 (63.3%) were male and 11 (36.7%) were female. The albumin level was lower in the patient group compared to the NPH group (3.8 g/dL [1.8–4.7] vs. 4.3 g/dL [3.2–5.0], respectively, p = 0.008). The serum IMA level was higher in the patient group compared to the NPH group (0.36 ABSU [0.30–0.65] vs. 0.25 ABSU [0.05–0.32], respectively, p = 0.010). The serum IMA level was higher in the vasospasm group compared to the group without vasospasm. Conclusions: In patients with SAH, a condition associated with high morbidity and mortality, modified albumin levels were found to be significantly higher in both CSF and blood compared to the NPH group. IMA may be a potential biomarker associated with SAH and vasospasm; however, further large-scale studies with multivariable analysis and external validation are required to confirm its diagnostic and prognostic utility.

Aims/hypothesisWe examined whether candidate biomarkers in serum or urine can improve the prediction of renal disease progression in type 1 diabetes beyond prior eGFR, comparing their performance with urinary albumin/creatinine ratio (ACR).MethodsFrom the population-representative Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) we sampled 50% and 25% of those with starting eGFR below and above 75 ml min−1 [1.73 m]−2, respectively (N = 1629), and with median 5.1 years of follow-up. Multiplexed ELISAs and single molecule array technology were used to measure nine serum biomarkers and 13 urine biomarkers based on our and others’ prior work using large discovery and candidate studies. Associations with final eGFR and with progression to <30 ml min−1 [1.73] m−2, both adjusted for baseline eGFR, were tested using linear and logistic regression models. Parsimonious biomarker panels were identified using a penalised Bayesian approach, and their performance was evaluated through tenfold cross-validation and compared with using urinary ACR and other clinical record data.ResultsSeven serum and seven urine biomarkers were strongly associated with either final eGFR or progression to <30 ml min−1 [1.73 m]−2, adjusting for baseline eGFR and other covariates (all at p<2.3 × 10−3). Of these, associations of four serum biomarkers were independent of ACR for both outcomes. The strongest associations with both final eGFR and progression to <30 ml min−1 [1.73 m]−2 were for serum TNF receptor 1, kidney injury molecule 1, CD27 antigen, α-1-microglobulin and syndecan-1. These serum associations were also significant in normoalbuminuric participants for both outcomes. On top of baseline covariates, the r2 for prediction of final eGFR increased from 0.702 to 0.743 for serum biomarkers, and from 0.702 to 0.721 for ACR alone. The area under the receiver operating characteristic curve for progression to <30 ml min−1 [1.73 m]−2 increased from 0.876 to 0.953 for serum biomarkers, and to 0.911 for ACR alone. Other urinary biomarkers did not outperform ACR.Conclusions/interpretationA parsimonious panel of serum biomarkers easily measurable along with serum creatinine may outperform ACR for predicting renal disease progression in type 1 diabetes, potentially obviating the need for urine testing.

Introduction Albumin kinetics in septic shock have been extensively studied, but clinical recommendations remain weak. An increased transcapillary escape rate (TER) of albumin has been demonstrated, though TER does not account for lymphatic return. Mass balance calculations, considering lymphatic return, have been used to assess net albumin leakage (NAL) in major surgery but not in sepsis. Objectives This study aimed to evaluate NAL in ten ICU patients with suspected sepsis, hypothesizing a net positive leakage. Secondary aims included investigating associations between NAL and fluid overload, glycocalyx shedding products, and cytokines, as well as identifying factors associated with it. Methods This prospective, observational study included ten patients within twelve hours of ICU admission for suspected sepsis at Karolinska University Hospital Huddinge. Albumin, hematocrit, and hemoglobin levels were sampled at 0, 1, 2, 4, 8, and 24 h. NAL was estimated using mass balance calculations, comparing proportional changes in albumin and hemoglobin concentrations over time, adjusted for albumin and hemoglobin infusions and losses. A proportionally greater decrease or smaller increase in albumin compared to hemoglobin indicated NAL, representing the net leakage from the circulation to the interstitium minus lymphatic return. Results Over 24 h, patients exhibited a net positive albumin leakage to the interstitium of 8 ± 10 g ( p  = 0.029). NAL showed no correlation with glycocalyx shedding products or fluid overload but had a weak correlation with interleukin-6 and interleukin-8 in the first 4 h. Albumin infusions appeared to increase net leakage. Conclusion This study demonstrated a net positive albumin leakage of 8 ± 10 g over 24 h in ICU patients with suspected sepsis, with a weak early correlation to pro-inflammatory cytokines but no significant link to fluid balance or glycocalyx shedding. Notably, albumin infusions were associated with increased net leakage.

BackgroundAlbumin-bilirubin (ALBI) grade is an objective measure of liver function for patients with hepatocellular carcinoma (HCC). The tyrosine kinase inhibitor cabozantinib is approved for patients with advanced HCC who have received prior sorafenib based on the phase 3 CELESTIAL trial (NCT01908426). Cabozantinib improved overall survival (OS) and progression-free survival (PFS) versus placebo in patients with previously treated HCC.MethodsPatients were randomised 2:1 to receive cabozantinib 60 mg or placebo orally every day. Clinical outcomes in patients with ALBI grade 1 or 2 at baseline were evaluated in CELESTIAL. ALBI scores were retrospectively calculated based on baseline serum albumin and total bilirubin, with an ALBI grade of 1 defined as  ≤ −2.60 score and a grade of 2 as a score of > −2.60 to  ≤ −1.39.ResultsCabozantinib improved OS and PFS versus placebo in both ALBI grade 1 (hazard ratio [HR] [95% CI]: 0.63 [0.46–0.86] and 0.42 [0.32–0.56]) and ALBI grade 2 (HR [95% CI]: 0.84 [0.66–1.06] and 0.46 [0.37–0.58]) subgroups. Adverse events were consistent with those in the overall population. Rates of grade 3/4 adverse events associated with hepatic decompensation were generally low and were more common among patients in the ALBI grade 2 subgroup.DiscussionThese results provide initial support of cabozantinib in patients with advanced HCC irrespective of ALBI grade 1 or 2.Trial registration numberClinicalTrials.gov number, NCT01908426.

Oral nutritional supplementation (ONS) is recommended for malnourished hemodialysis patients when their nutritional intake remains inadequate to meet energy and protein requirements. Patients were randomized into two groups: the intradialytic ONS supplements (INTRA-ONS) group (N = 16) and the interdialytic ONS supplements (INTER-ONS) group (N = 16) for a duration of 12 weeks. Malnutrition inflammation score (MIS) and serum albumin levels were assessed. The total MIS decreased significantly in patients from both the INTRA-ONS group (− 6.13, 95% CI − 8.29 to − 3.96) and the INTER-ONS group (− 3.50, 95% CI − 5.56 to − 1.35). A significant difference in the change of MIS was observed between the two groups (− 3.06, 95% CI − 5.94 to − 0.17). No significant differences were observed between the groups concerning serum albumin levels, dietary intake, anthropometric measurements, or body weight. Intradialytic ONS demonstrates similar benefits on nutritional biomarkers but improves the MIS among malnourished ESRD patients compared to interdialytic ONS. Trial registration Thai Clinical Trials Registry (TCTR) identification number is TCTR20220322007: 16/09/2021.

Background and Objectives: The neutrophil-percentage-to-albumin ratio (NPAR) has been recognized as an independent risk factor for cardiovascular diseases. In our study, we investigated whether the NPAR is associated with the formation of coronary collateral circulation (CCC) in patients with chronic coronary syndrome (CCS). Materials and Methods: A total of 681 patients with CCS were included in this study. Of these patients, 571 had chronic total occlusion in at least one major vessel and developed collateral vessels. In total, 110 patients were in the control group, who had CCS but did not have complete occlusion in a major vessel and did not develop collateral vessels. Patients with collateral vessels on coronary angiography were divided into two groups according to the Rentrop score: poor CCC (Rentrop 0–1) and good CCC (Rentrop 2–3). Blood samples were taken for the NPAR and other biochemical parameters in all patients during hospitalization. The NPAR was calculated as the neutrophil-percentage-to-albumin ratio. Results: The group of patients with poor CCC had a higher white blood count (WBC), neutrophil, C-reactive protein (CRP), neutrophil–lymphocyte ratio (NLR), CRP/albumin ratio (CAR), and NPAR values than patients with good CCC (p < 0.001, for all). Multivariate logistic regression analysis showed that high NPAR levels were an independent predictor of poor CCC (OR: 2.79, 95% CI:1.7–4.6, p < 0.001), accompanied by neutrophil, CRP, CAR, and NLR levels. In the receiver operator characteristic curve (ROC analysis), the cut-off value for the NPAR to indicate poor CCC was 1.78 with a sensitivity of 76.6% and specificity of 81.4% (area under ROC curve = 0.804 95% CI (0.753–0.854), p < 0.001). Conclusions: We demonstrated that the NPAR may be an independent predictor of poor CCC development in clinical practice.